Article: article from journal or magazin.
Common human genetic variants and HIV-1 susceptibility: a genome-wide survey in a homogeneous African population.
Publication types: Journal Article ; Research Support, N.I.H., ExtramuralPublication Status: ppublish
Objective: To date, CCR5 variants remain the only human genetic factorsto be confirmed to impact HIV-1 acquisition. However, protective CCR5variants are largely absent in African populations, in which sporadicresistance to HIV-1 infection is still unexplained. We investigatedwhether common genetic variants associate with HIV-1 susceptibility inAfricans.Methods: We performed a genome-wide association study (GWAS) in apopulation of 1532 individuals from Malawi, a country with highprevalence of HIV-1 infection. Using single-nucleotide polymorphisms(SNPs) present on the genome-wide chip, we also investigated previouslyreported associations with HIV-1 susceptibility or acquisition.Recruitment was coordinated by the Center for HIV/AIDS VaccineImmunology at two sexually transmitted infection clinics. HIV status wasdetermined by HIV rapid tests and nucleic acid testing.Results: After quality control, the population consisted of 848high-risk seronegative and 531 HIV-1 seropositive individuals. Logisticregression testing in an additive genetic model was performed for SNPsthat passed quality control. No single SNP yielded a significant P valueafter correction for multiple testing. The study was sufficientlypowered to detect markers with genotype relative risk 2.0 or more andminor allele frequencies 12% or more.Conclusion: This is the first GWAS of host determinants of HIV-1susceptibility, performed in an African population. The absence of anysignificant association can have many possible explanations: rarergenetic variants or common variants with weaker effect could beresponsible for the resistance phenotype; alternatively, resistance toHIV-1 infection might be due to nongenetic parameters or to complexinteractions between genes, immunity and environment. (C) 2011 WoltersKluwer Health vertical bar Lippincott Williams & Wilkins
Adolescent, Adult, African Continental Ancestry Group/genetics, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, HIV Infections/epidemiology, HIV Infections/genetics, HIV-1, Humans, Type="Geographic">Malawi/epidemiology, Male, Middle Aged, Phenotype, Receptors, CCR5/genetics, Young Adult
Web of science
Last modification date